Carboxy-Terminal Cementum Protein 1-Derived Peptide 4 (cemp1-p4) Promotes Mineralization through wnt/β-catenin Signaling in Human Oral Mucosa Stem Cells
| Autor: | Gonzalo Montoya, Claudia Pedraza, Yonathan Garfias, Lía Hoz, Enrique Romo, Higinio Arzate, Sonia López, Rita Arroyo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Bone Regeneration Cellular differentiation Core Binding Factor Alpha 1 Subunit Protein Structure Secondary lcsh:Chemistry 0302 clinical medicine Osteogenesis β-catenin mineralization lcsh:QH301-705.5 Wnt Signaling Pathway Spectroscopy Dental Cementum Chemistry Wnt signaling pathway Gene Expression Regulation Developmental Osteoblast Cell Differentiation General Medicine musculoskeletal system peptide Computer Science Applications Cell biology RUNX2 medicine.anatomical_structure Sp7 Transcription Factor Signal transduction cementum musculoskeletal diseases Periodontal Ligament Cementoblast Osteocalcin Catalysis Article Inorganic Chemistry 03 medical and health sciences stomatognathic system stem cells medicine Humans Integrin-Binding Sialoprotein Physical and Theoretical Chemistry Molecular Biology Transcription factor Cell Proliferation Glycogen Synthase Kinase 3 beta Osteoblasts Organic Chemistry Mouth Mucosa Proteins 030206 dentistry 030104 developmental biology Durapatite lcsh:Biology (General) lcsh:QD1-999 Peptides Lymphoid enhancer-binding factor 1 CEMP1-p4 |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 4 International Journal of Molecular Sciences, Vol 21, Iss 4, p 1307 (2020) |
| ISSN: | 1422-0067 |
| Popis: | Human cementum protein 1 (CEMP1) is known to induce cementoblast and osteoblast differentiation and alkaline phosphatase (ALP) activity in human periodontal ligament-derived cells in vitro and promotes bone regeneration in vivo. CEMP1&prime s secondary structure analysis shows that it has a random-coiled structure and is considered an Intrinsic Disordered Protein (IDP). CEMP1&prime s short peptide sequences mimic the biological capabilities of CEMP1. However, the role and mechanisms of CEMP1&prime s C-terminal-derived synthetic peptide (CEMP1-p4) in the canonical Wnt/&beta catenin signaling pathway are yet to be described. Here we report that CEMP1-p4 promotes proliferation and differentiation of Human Oral Mucosa Stem Cells (HOMSCs) by activating the Wnt/&beta catenin pathway. CEMP1-p4 stimulation upregulated the expression of &beta catenin and glycogen synthase kinase 3 beta (GSK-3B) and activated the transcription factors TCF1/7 and Lymphoid Enhancer binding Factor 1 (LEF1) at the mRNA and protein levels. We found translocation of &beta catenin to the nucleus in CEMP1-p4-treated cultures. The peptide also penetrates the cell membrane and aggregates around the cell nucleus. Analysis of CEMP1-p4 secondary structure revealed that it has a random-coiled structure. Its biological activities included the induction to nucleate hydroxyapatite crystals. In CEMP1-p4-treated HOMSCs, ALP activity and calcium deposits increased. Expression of Osterix (OSX), Runt-related transcription factor 2 (RUNX2), Integrin binding sialoproptein (IBSP) and osteocalcin (OCN) were upregulated. Altogether, these data show that CEMP1-p4 plays a direct role in the differentiation of HOMSCs to a &ldquo mineralizing-like&rdquo phenotype by activating the &beta catenin signaling cascade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|